nAChR Isoform | Competitive Antagonist | ℓ+1 Onset (×108 M−1s−1) | ℓ−1 Onset (s−1) | ℓ−1 Recovery (s−1) | ℓ−1/ℓ+1 Rec./Onset (nM) | ℓ′−1 O + OD (s−1) |
---|---|---|---|---|---|---|
Adult | cisatr | 1.8 ± 0.32-a | 18.0 ± 142-a | 12.6 ± 4.82-a | 71 ± 292-a | 32.9 ± 5.3ab |
−50 mV | (12) | (12) | (12) | (36) | ||
Embryonic | cisatr | 3.4 ± 0.3 | 40.9 ± 19 | 34.2 ± 6.2 | 101 ± 22 | 52.0 ± 9.32-b |
−50 mV | (12) | (12) | (15) | (11) | ||
Embryonic | cisatr | N.A. | N.A. | 30.9 ± 2.3 | N.A. | N.A. |
+50 mV | (5) | |||||
Embryonic | (+)-Tubocurarine | 1.2 ± 0.22-c | 6.5 ± 2.22-c | 5.9 ± 1.32-c | 50 ± 152-c | N.A. |
−50 mV | (11) | (11) | (8) | |||
Embryonic | Pancuronium | 2.7 ± 0.92-c | 1.9 ± 1.22-c | 2.1 ± 0.72-c | 7.8 ± 3.72-c | N.A. |
−50 mV | (14) | (14) | (12) |
The association (ℓ+1 Onset) and dissociation (ℓ−1Onset) rate constants in the absence of ACh determined with the onset protocol, dissociation rate constant in the absence of ACh (ℓ−1 Recovery) determined with the recovery protocol, the calculated equilibrium constant in the absence of ACh (ℓ−1Recovery/ℓ+1 Onset), and the dissociation rate constant in the presence of ACh (ℓ′−1 O + OD) determined with the O + OD protocol for cisatr on embryonic and adult receptors are reported as mean ± S.D.; the number of data points are included within parentheses. The last two rows refer to the kinetics of (+)-tubocurarine and pancuronium in the absence of ACh from Wenningmann and Dilger (2001).
Multiple statistical comparisons were performed within and between rows (see Results):
↵2-a , p < 0.003 for comparison of cisatr kinetics on adult receptors with those on embryonic receptors (−50 mV).
↵2-b , p < 0.0001 for comparison of ℓ′−1 with ℓ−1.
↵2-c , p < 0.01 for comparison of the kinetics of cisatr with those of (+)-tubocurarine and pancuronium on embryonic receptors using one-way analysis of variance Student-Newman-Keuls multiple comparisons test. The values of ℓ−1 of cisatr from embryonic receptors were not significantly different at −50 and +50 mV. The values of ℓ−1/ℓ+1 of cisatr from adult and embryonic receptors were not significantly different than their corresponding IC50 values (Table 1).